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quinolones

How do quinolones work?

Posed on  November 26, 2020, edited by Jason, category  
quinolones
quinolones

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What are quinolones?

1. Definition

Quinolones, also known as pyridone acids, are synthetic antibacterial drugs containing the basic structure of 4-quinolones. Quinolones target bacterial deoxyribonucleic acid (DNA), hinder DNA gyrase, and further cause irreversible damage to bacterial DNA to achieve antibacterial effects.

In 1979, Norfloxacin was synthesized, and then a series of fluorine-containing new quinolones were synthesized, commonly known as fluoroquinolones. Quinolone drugs are divided into four generations, and the third generation is widely used. Commonly used drugs include norfloxacin, ofloxacin, ciprofloxacin, fleroxacin, etc. These drugs have bactericidal effects on a variety of Gram-negative bacteria, and are widely used in the treatment of genitourinary system diseases, gastrointestinal diseases, and the treatment of gram-negative bacterial infections in the respiratory tract and skin tissues.

2. Antibacterial mechanism

The target enzymes of quinolone drugs are bacterial DNA gyrase and topoisomerase IV. For most gram-negative bacteria, DNA gyrase is the main target enzyme for quinolones. For most gram-positive bacteria, quinolones mainly inhibit the bacterial topoisomerase IV, which is a helicase that can release the entangled progeny chromosomes during DNA replication.

3. Features

It has a strong antibacterial effect and a broad antibacterial spectrum. It mainly fights against Gram-negative bacteria and also has a considerable effect on Gram-positive bacteria. It is widely distributed in the body and can enter bones, joints and prostate tissues that most drugs cannot enter. Quinolones rarely develop resistance by themselves, and there is no cross-resistance with other antibacterial drugs, which is conducive to the combination of other antibiotics.

  • Broad antibacterial spectrum, especially for aerobic gram-negative bacilli, including Pseudomonas aeruginosa, has a strong bactericidal effect, and a good antibacterial effect on Staphylococcus aureus and enzyme-producing Staphylococcus aureus. Certain species also have effects on tuberculosis, mycoplasma, chlamydia and anaerobic bacteria.
  • It performs well taken orally and is widely distributed in the body. The plasma protein binding rate is low, and the plasma half-life is relatively long. Part of it is excreted through the kidneys in its original form, with high urine concentration, and other parts are metabolized by the liver.
  • It has few adverse reactions and well toleration. Nausea, vomiting, loss of appetite, rash, headache and dizziness can be seen. Occasionally, there are mental symptoms such as convulsions, which can be resolved by stopping the drug. All fluoroquinolones can cause joint disease in juvenile animals and joint pain and swelling in children, so they should not be used in prepubescent children or pregnant women.
  • It is suitable for urinary infections caused by sensitive pathogens (such as Staphylococcus aureus, Pseudomonas aeruginosa, intestinal gram-negative bacilli, Campylobacter and Neisseria gonorrhoeae, etc.), prostate infections, gonorrhea, respiratory infections, gastrointestinal tract Infection and bone, joint, and soft tissue infection.
  • A class of drugs that can act on the deoxyribonucleic acid (DNA) of bacteria and cause irreversible damage to bacterial chromosomes. Because of the different structure and mechanism of action of these drugs, there is no cross-resistance within antibiotics. It mainly acts on negative bacteria, and have weak effects on positive bacteria except Staphylococcus aureus. Commonly used varieties includ pipemidic acid, norfloxacin, norfloxacin, and ciprofloxacin.
  • Adverse reactions include:
    • Gastrointestinal reactions with nausea and other discomforts.
    • Central reactions can cause psychiatric symptoms and also induce epilepsy.
    • It can affect cartilage development, so pregnant women and underage children should use it with caution.
    • Sometimes allergic reactions such as skin rashes may appear.
    • Long-term heavy use can cause liver damage.

4. Drug Interactions

  • Alkaline drugs, anticholinergic drugs, and H2 receptor blockers can reduce the acidity of gastric juice and the absorption of these drugs. So avoid taking them together.
  • Both rifampicin (RNA synthesis inhibitor) and chloramphenicol (protein synthesis inhibitor) can reduce the effect of this class of drugs, make the effects of nalidixic acid and norfloxacin completely disappear, and partially offset the effect of fluoxinic acid and ciprofloxacin.
  • Fluoroquinolones inhibit the metabolism of theophylline. When combined with theophylline, the blood concentration of theophylline will increase, and theophylline's toxic reaction may occur, so attention should be paid.

Quinolone classification

Quinolones are divided into first, second, third and fourth generations according to the order of invention and their antibacterial properties.

  1. The first-generation quinolones have antibacterial effects only against Escherichia coli, Shigella, Klebsiella, and a few Proteus. Specific varieties include nalidixic acid and pyrrolic acid, etc., which have been weeded out due to poor efficacy.
  2. The second-generation quinolones have expanded their antibacterial spectrum and have certain antibacterial effects against Enterobacter, Citrobacter, Pseudomonas aeruginosa, and Serratia. Pipemidic acid is mainly domestically applied. In addition, there are Cinoxacin and Miloxacin, which are produced abroad. Because their side effects are fundamental, except for pipemidic acid, others have been eliminated.
  3. The antibacterial spectrum of the third-generation quinolones is further expanded, and it also has antibacterial effect on gram-positive bacteria such as staphylococci, and its antibacterial effect on some gram-negative bacteria is further enhanced. Main products include Norfloxacin, Ofloxacin, Levofloxacin, Pefloxacin, Enoxacin, Ciprofloxacin and so on. There are fluorine atoms in the molecules of this generation of drugs. Therefore, it is called fluoroquinolone.
  4. Compared with the previous three generation drugs, the fourth-generation quinolones are structurally modified. The introduction of 8-methoxyl groups in the structure helps to strengthen the anti-anaerobe activity, while the nitro-dioxy ring structure at the C-7 position strengthens the anti-gram-positive bacteria activity and maintains the original anti-Gram-negative bacteria activity.

The adverse reactions are smaller, but the price is more expensive. It has enhanced antibacterial activity against gram-positive bacteria, enhanced effect on anaerobic bacteria including Bacteroides fragilis, and typical pathogens such as Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella and Mycobacterium tuberculosis. Most products have prolonged half-life, such as gatifloxacin, trovafloxacin, clinfloxacin, and moxifloxacin.

How do quinolones work?

1. Principle of action

The basic skeletons of quinolone antibiotics are all nitrogen (hetero) double cyclic structures. Quinolones and other antibacterial drugs have different points of action. They target bacterial deoxyribonucleic acid (DNA). The double-stranded DNA of bacteria is twisted into loops or spirals (called supercoils). The enzyme that makes the DNA supercoils is called DNA gyrase. Quinolones hinder this enzyme and further cause irreversible damage to the bacterial DNA, so that the cells cannot divide. They show selective toxicity to bacteria.

At present, the resistance of some bacteria to many antibiotics can spread widely due to plasmid transmission. This class of drugs is not affected by plasmid-transmitted drug resistance. Therefore, there is no cross-resistance between this class of drugs and many antibacterial drugs.

Quinolones are antibacterial drugs that mainly act on gram-negative bacteria and have weaker effects on gram-positive bacteria (some varieties have better antibacterial effects on Staphylococcus aureus).

2. Application

Quinolone antibiotics are a class of drugs commonly used by humans and animals. Because of their wide antibacterial spectrum, strong antibacterial activity, no cross-resistance with other antibacterial drugs, and low side effects, they are widely used in disease control of livestock, aquaculture and other breeding industries, including chickens, ducks, geese, pigs, cattle, Sheep, fish, shrimp, crab, etc.

Enrofloxacin, a kind of fluoroquinolone antibiotics, has the characteristics of wide antibacterial spectrum, strong bactericidal power, rapid action, wide distribution in the body and no cross-resistance with other antibiotics. It prevents and treats bacterial infections and mycoplasmosis in livestock and poultry.

In the prevention and control of pig diseases, they are also effective against Pseudomonas aeruginosa, Klebsiella, Escherichia coli, Enterobacter, Campylobacter, Shigella, Salmonella, Aeromonas Gram-negative bacilli and cocci including genus, Haemophilus, Yersinia, Serratia, Vibrio, Proteus, Brucella, Pasteurella Genus, Erysipelas, Bordetella, Staphylococcus, Mycoplasma and Chlamydia.

In addition, it has good effects on synergistic sulfa-resistant bacteria, gentamicin-resistant Pseudomonas aeruginosa, penicillin-resistant Staphylococcus aureus, and tylosin or tiamulin-resistant Mycoplasma.

3. Fluoroquinolones Side effects

  • Gastrointestinal reactions: nausea, vomiting, discomfort, pain, etc.;
  • Central reactions: headache, dizziness, poor sleep, etc., causing mental symptoms;
  • Because this class of drugs can inhibit the effect of γ-aminobutyric acid (GABA), it can induce epilepsy, so those with a history of epilepsy should use them with caution;
  • This class of drugs can affect cartilage development, so pregnant women and underage children should use them with caution;
  • Crystaluria can be produced, especially in alkaline urine;
  • Large-dose or long-term application of this type of drugs can easily cause liver damage.

The future of quinolones

1. Hidden danger

Quinolone drugs are widely used in the treatment of human and animal diseases. Due to the residues of quinolone drugs in animal tissues, quinolone antibiotics accumulation in the human body after human consumption of animal tissues, they can result in severe resistance to human diseases. The medicinal properties affect the treatment of human diseases. As the saying goes, medicine is poison in one way. Long-term intake of animal-derived foods containing quinolones is pernicious to the human body.

Long-term consumption of animal foods and Chinese patent medicine health foods containing low concentrations of QNs drugs can easily induce the transmission of drug resistance, thereby affecting the clinical efficacy of such drugs. Therefore, the problem of quinolone residues has attracted more and more attention. The Joint Committee of Food Additives Experts of the Food and Agriculture Organization of the United Nations and the World Health Organization and the European Union have established maximum residue limits for various quinolones in animal tissues. The US FDA announced in 2005 that the use of enrofloxacin, an antibacterial drug used to treat bacterial infections in poultry, was banned.

China also stipulated in 2002 the highest level of 7 QNs drugs including ciprofloxacin, danofloxacin, enrofloxacin, sarafloxacin, difloxacin, oxolinic acid and flumequine in animal muscle tissues is 10~500μg/kg. The main analytical methods of quinolones residues in animal tissues are enzyme-linked immunosorbent assay (EL ISA), high performance liquid chromatography (HPLC) and liquid chromatography 2 mass spectrometry (LC2MS).

2. Outlook

Quinolones, broad-spectrum antibacterial drugs, are mainly used for the treatment of human diseases. In order to avoid harm to the human body caused by consumption of animal foods containing quinolone residues, it is necessary to develop animal-specific quinolone drugs.

For animals specially, there are sarafloxacin, enrofloxacin, danofloxacin, marbofloxacin, orbifloxacin, danofloxacin and so on. Danoxacin is used to treat diseases caused by bacteria and mycoplasma in cattle, pigs, chickens and other animals, and has good antibacterial effect on the main pathogenic bacteria in the respiratory tract. Orbifloxacin is used to treat pneumonia and diarrhea in pigs and cattle.

However, it is necessary to evaluate the safety of animal-specific quinolones for humans.

Conclusion

Quinolones have a broad antibacterial spectrum and strong antibacterial effect. Coupled with the special mechanism of action of quinolones, it can be used with other antibiotics without worrying about the drug resistance.

quinolones test
quinolones test

BALLYA provides a Quinolones Rapid Test Kit to tell you if there is quinolones residues in dairy products you eat every day.

References

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